Endoscopic cryoablation catheter

ABSTRACT

A cryoablation device is provide herein which, in an embodiment, includes a catheter shaft and a cryogen return line disposed within the catheter shaft. A cryogen supply line is disposed within the cryogen return line, such that the cryogen supply line, the cryogen return line, and the catheter shaft are all substantially coaxial. A needle tip probe is disposed at a distal end of the cryogen return line and the cryogen supply line extends in a distal direction beyond a distal end of the cryogen return line and into the needle tip probe. An insulating tube is disposed circumferentially around the cryogen return line and within the catheter shaft. An insulating lumen is circumferentially disposed around the return line, between an inner diameter of the catheter shaft and an outer diameter of the insulating tube. A position of the insulating tube is fixed relative to the catheter shaft. A position of the needle tip probe and the cryogen return line is axially and rotationally movable with respect to the insulating tube and the catheter shaft.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of co-pending U.S.application Ser. No. 15/881,441, filed Jan. 26, 2018, which was acontinuation-in-part of U.S. application Ser. No. 13/937,658, filed Jul.9, 2013 and issued as U.S. Pat. No. 9,877,767 on Jan. 30, 2018, whichclaims the benefit of U.S. Application No. 61/783,488, filed Mar. 14,2013. Each of the foregoing US patent applications is incorporated byreference as though fully set forth herein.

FIELD OF THE INVENTION

The present invention relates generally to medical devices, and, inparticular, to a surgical catheter for cryoablation.

BACKGROUND OF THE INVENTION

Pancreatic cancer is one of the major causes of cancer death in Westerncountries. In 2010, an estimated 43,140 new cases of pancreatic cancerwere diagnosed in the United States with an expected five year survivalrate of less than about 10%. In about 20% of patients with nometastases, tumor resection is not feasible because of vascularinvasion, poor general health, or lacking surgical techniques. Thestandard treatment for these patients is chemotherapy followed bychemo-radiation therapy, which results in a median survival of eight totwelve months or less.

Current therapeutic options for unresectable pancreatic cancer includeradiofrequency ablation (RFA) and cryotherapy. As utilized in thetreatment of pancreatic cancer, RFA risks thermal injury to importantstructures such as the bile duct, the duodenum, and vessels close to thepancreas. A major limitation with RFA is difficulty in assessing theablated zone by ultrasound, magnetic resonance imaging (MRI) or computedtomography (CT) scan. The poorly perfused pancreatic area also makes itdifficult to visualize. Further, studies have demonstrated thatradiologic follow-up after ablation could not distinguish inflammatoryreactions of the tumor tissue from tumor growth or necrosis within thefirst four weeks.

Studies have shown the effective use of cryoablation to treat pancreaticcancer via laparoscopic or transcutaneous approach with reduced sideeffects. Yet, broad based clinical utilization has been limited bycommercial devices that do not provide adequate cooling power toeffectively treat the cancerous tissue. The invasive nature of surgical(open or laparoscopic) access to the target also remains an ongoingissue along with technological limitations.

In addition, current cryoprobes as used in an endoscopic procedure cancause damage to the endoscope due to freezing of the catheter shaft tothe inside of the endoscope. This can interfere with the ultrasoundimaging and readjusting or removing the cryoprobe from the tissue orendoscope in a timely manner. Prolonged procedures also can causefreezing of the endoscope to surrounding tissue resulting in damage tonon-target tissues such as the esophagus, stomach wall, colon,intestine, rectum or other structure.

For visualization of current pancreatic procedures, endoscopicultrasound (EUS) has been utilized to image the pancreas in real-time.Issues related to laparoscopic ablation techniques, however, makeimaging difficult. For example, anatomical location of the pancreasmakes it difficult to visualize and access without damaging othertissues.

SUMMARY OF THE INVENTION

A first aspect of the invention provides an endoscopic cryoablationdevice comprising a catheter shaft; a cryogen return line disposedwithin the catheter shaft; and a cryogen supply line disposed within thecryogen return line, such that the cryogen supply line, the cryogenreturn line, and the catheter shaft are all substantially coaxial. Aneedle tip probe is affixed to a distal end of the cryogen return line.The cryogen supply line extends in a distal direction beyond a distalend of the cryogen return line and into the needle tip probe, and thecatheter shaft is axially movable relative to the needle tip probe andthe cryogen return line, and the catheter shaft is configured such thatthe catheter shaft is distally extended over the needle tip probe in anextended position.

A second aspect of the invention provides an endoscopic cryoablationdevice comprising: a catheter shaft; a cryogen return line disposedwithin the catheter shaft; a cryogen supply line disposed within thecryogen return line, such that the cryogen supply line, the cryogenreturn line, and the catheter shaft are all substantially coaxial; andan insulating lumen circumferentially disposed around the return line,between an inner diameter of the catheter shaft and an outer diameter ofthe return line. A needle tip probe is disposed at a distal end of thecryogen return line, and the cryogen supply line extends in a distaldirection beyond a distal end of the cryogen return line and into theneedle tip probe.

A third aspect of the invention provides a cryoablation devicecomprising: a catheter shaft; a cryogen return line disposed within thecatheter shaft; a cryogen supply line disposed within the cryogen returnline, such that the cryogen supply line, the cryogen return line, andthe catheter shaft are all substantially coaxial; a needle tip probedisposed at a distal end of the cryogen return line, wherein the cryogensupply line extends in a distal direction beyond a distal end of thecryogen return line and into the needle tip probe; an insulating tubedisposed circumferentially around the cryogen return line and within thecatheter shaft, and an insulating lumen circumferentially disposedaround the return line, between an inner diameter of the catheter shaftand an outer diameter of the insulating tube, wherein a position of theinsulating tube is fixed relative to the catheter shaft, and wherein aposition of the needle tip probe and the cryogen return line is axiallyand rotationally movable with respect to the insulating tube and thecatheter shaft.

Various aspects of the invention describe a cryoablation deviceintegrated with an endoscope that facilitates rapid and effectivetreatment of pancreatic cancer or other gastrointestinal cancers orunwanted tissues.

In one embodiment, a cryoablation device provides a rapid and effectivemethodology to treat pancreatic cancer endoscopically. Endoscopic accessin combination with targeted ablative techniques reduces procedure time,overall costs, and risks associated therewith. The improved endoscopiccryoablation device implements a cryoablation catheter compatible foruse within an endoscope. The cryoablation catheter has the flexibility,stiffness, and steerability to place a probe tip located thereindirectly though the stomach wall and into a pancreatic tumor. Thecryoablation catheter is also compatible with any other type ofendoscope or colorectal scope for which its introduction and placementcan be guided by any other type of visualization technique, includingbut not limited to external ultrasound, fluoroscopy, CT, MRI, opticaland/or video assisted visualization. The sharp needle-like tip of theprobe is capable of penetrating any desmoplasia, fibrous connectivetissue, tumor infiltrate, and scar or fibrosis, even in patients whohave already undergone radiation therapy. Additionally, the sharpness ofthis needle-like probe is utilized for EUS guided pseudocyst drainageduring the procedure.

One embodiment of the endoscopic cryoablation catheter incorporates acryoablation procedure which provides surgeons with a minimally invasivetool that reduces patient morbidity and lowers costs as compared tolaparoscopic or surgical procedures. The method of using the apparatusfor endoscopic ablation therapy comprises the steps of: providing anapparatus comprising a cryogen supply line and a cryogen return linesurrounded by a catheter shaft, such that the cryogen supply line, thecryogen return line, and the catheter shaft run longitudinally from aproximal end at a cryogen console to a distal end at an ablation zone;wherein the distal end of the catheter shaft interconnects with ahandle; inserting the catheter shaft into an endoscopic path, whereinthe shaft covers the ablation zone; positioning the ablation zone to atissue site; retracting the catheter shaft to expose the ablation zone;delivering cryogenic temperatures to the ablation zone for an allocatedtreatment time; allowing the ablation zone to thaw or heat; removing theablation zone from the tissue site; protracting the sheath to cover theablation zone; and removing the catheter shaft from the endoscopic path.In particular, the endoscopic cryoablation catheter is designed for usein treating pancreatic cancer in vivo. When positioning the ablationzone, or probe tip, the apparatus is directed through an endoscopic paththat enters the stomach. The probe tip is a needle-tip probe that isinserted through a wall of the stomach and directed into the pancreatictissue. Any number of procedures may be performed at a single treatmentsite or at various sites within or along an endoscopic path. Where aheating element such as a heating coil is utilized during thaw or activeheat ablation, the tissue site can be further damaged. Further, theactive heat ablation may be used to cauterize tissue at the treatmentsite or anywhere along the endoscopic path. As mentioned in detail inthe following, any step during the procedure can be motorized,computerized, and/or programmed prior to, during, or following aprocedure step in the methodology.

In one embodiment, the endoscopic cryoablation catheter is utilized incombination with other anti-cancer therapies including radiation, RF,chemotherapy, gene therapy, or any other treatment modality insimultaneous or staged delivery.

Furthermore, endoscopic access coupled with targeted in situ cancerdestruction reduces procedure time, overall costs, and risks ofcomplication while offering an effective therapeutic option currentlyunavailable to pancreatic cancer patients

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various embodiments of thepresent invention, and, together with the description, serve to explainthe principles of the invention. The various features are notnecessarily drawn to scale. In fact, the dimensions may be arbitrarilyincreased or decreased for clarity of discussion. In the drawings:

FIG. 1 is an external perspective view of an illustrative embodiment ofthe invention.

FIG. 2 is a magnified transparent side view of a distal end of anembodiment of the invention with a covered probe tip.

FIG. 3 is a magnified transparent side view of a distal end of anembodiment of the invention with the cover sheath retracted.

FIG. 4A is magnified view of an embodiment of the invention such thatthe probe at the distal end is covered by the sheath.

FIG. 4B depicts an embodiment of the invention with the sheathretracted.

FIG. 4C is a cut-away cross section of an embodiment of the inventionfrom FIG. 4A.

FIG. 5 is an embodiment of the invention with an internal view of thecomponents in the handle portion.

FIGS. 6-7 are illustrations of a device according to an embodiment ofthe invention, in the extended and retracted positions, respectively,including a needle-tip probe affixed to an outer wall of the cryogenreturn line, in an extended position.

FIG. 8 is a cross sectional illustration of a cryoablation catheterdevice, according to an embodiment of the invention.

FIGS. 9-10 are illustrations of a device according to an embodiment ofthe invention, in the extended and retracted positions, respectively,including a needle-tip probe affixed to an inner wall of the cryogenreturn line, in an extended position.

FIGS. 11-12 are illustrations of a device according to an embodiment ofthe invention, in the extended and retracted positions respectively,including a needle-tip probe affixed to an inner wall of the returnline, with an insulated tube disposed over the return line.

FIGS. 13-14 are illustrations of a device according to an embodiment ofthe invention, in extended and retracted positions respectively,including insulation disposed at a proximal end of the needle tip probe,and an insulated tube disposed about the return line.

FIG. 15 is an embodiment of the invention with an internal view of thecomponents in the handle portion depicting the return tube and catheteraffixed to various locations within the handle.

FIGS. 16-17 are illustrations of a device according to an embodiment ofthe invention, in the extended and retracted positions, respectively,including a needle-tip probe affixed to an outer wall of the cryogenreturn line, and the return line and needle probe disposed within aninsulated catheter shaft.

FIGS. 18-19 are illustrations of a device according to an embodiment ofthe invention, in the extended and retracted positions, respectively,including a needle-tip probe affixed to an outer wall of the cryogenreturn line, the return line, needle probe and accessory channeldisposed within an insulated catheter shaft.

FIG. 20 is a cross sectional illustration of a cryoablation catheterdevice, according to an embodiment of the invention with an insulatedcatheter shaft.

FIGS. 21-22 are illustrations of a device according to an embodiment ofthe invention, in the extended and retracted positions respectively,including a needle-tip probe affixed to an outer wall of the returnline, with an insulated tube disposed around the return line wherein theinsulative tube is affixed to the catheter.

FIGS. 23-24 are illustrations of a device according to an embodiment ofthe invention, in extended and retracted positions respectively,including insulation disposed at a proximal end of the needle tip probe,with an insulated tube disposed around the return line wherein theinsulative tube is affixed to the catheter.

DETAILED DESCRIPTION

Disclosed herein is an endoscopic cryoablation apparatus for theablation of undesirable tissue. A method of utilizing the endoscopiccryoablation apparatus to treat pancreatic cancer, gastrointestinalcancer, or other such tissue is also incorporated.

In describing the invention, reference will be made to variousembodiments, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same or like reference numbers will beused throughout the drawings to refer to the same or like parts.

A. Cryoablation Catheters Having a Sheath

As illustrated in FIG. 1, the endoscopic cryoablation apparatus 100comprises a cryoprobe tip 102 with an ablation zone 122 and integratedwith a catheter shaft 104 such that a moveable sheath 103 covers andexposes the cryoprobe tip 102 by way of a controllable handle 105. Asdepicted, an umbilical 110 has an outer wall 107 and attaches to aconnector 113 at a proximal end of the endoscopic cryoablation apparatus100. The connector interconnects with a cryo-system, or cryogenicconsole (not depicted) to deliver cryogenic fluid to the cryoprobe tip102. At a distal end, the cryoprobe tip 102 interconnects with aflexible catheter shaft 104. The flexible catheter shaft 104 has apolymeric composition with a diameter of between about 1 mm-5 mm,typically less than about 3.8 mm in diameter; and a length of betweenabout 0.5 m-2 m, typically between about 0.5 m-1.5 m. The catheter shaft104 can be safely passed through an operative channel of a therapeuticechoendoscope as desired. The overall longitudinal length of theapparatus 100 is between about 3 m to 6 m, or smaller, e.g., in therange of between about 1 m to 3 m. The diameter of the apparatus 100varies along its longitudinal axis and may be between about 1 mm toabout 10 mm, and even smaller, e.g., in the range of about 1 mm to about3 mm.

In one embodiment, the catheter shaft 104 extends through the handle 105and attaches to the umbilical 110 via retraction guide 109, which may bein the form of a transitional rigid portion. The retraction guide 109may be plastic, and may be configured to attach the catheter shaft 104to the umbilical 110. The handle 105 is fixed to move in the x-ydirectional plane across the retraction guide 109 but may also becapable of rotational movement around the catheter shaft 104 andretraction guide 109. A protective outer sheath 103 covers a distal endof the catheter shaft 104 between the handle 105 and a needle probe tip102. The sheath 103 is open-ended at the distal end to expose the needleprobe tip 102 for penetration into a target tissue when the sheath 103is retracted. The sheath 103 interconnects with the handle 105 forsynchronous control, movement and retraction. The retraction guide 109assists in translational movement of the handle 105 to move the sheath103 translationally along the x-y directional axis of the catheter shaft104. The sheath extends a length of between about 1 m to about 2 mbetween the handle 105 and the probe tip 102, as dependent on the lengthof the catheter shaft from the probe tip 102 to the handle 105. Thehandle is typically about 10 cm in length with a diameter between about1 mm to about 5 mm and larger so that a catheter of that size anddimension can be positioned within.

FIGS. 2 and 3 illustrate the distal end of the endoscopic cryoablationcatheter 100 such that cryogen supply line 106 and cryogen return line108 are housed in the catheter shaft 104. The catheter shaft isinsulated by heating elements 112. A lumen 126 between the return lineand catheter shaft provides an insulative layer to prevent freezing atan area external to the cryogen supply and return lines.

As shown in FIG. 2, the sheath 103 is protracted when the handle ismoved or pushed toward the distal end of the apparatus 100 (asdesignated by the arrow ‘x’). As shown in FIG. 3, retraction of thesheath exposes the probe tip 102 when the handle 105 is moved away fromthe distal end of the probe (as designated by the arrow ‘y’).

In addition, the catheter shaft 104 and umbilical 110 (see FIG. 1) areinsulated throughout their respective lengths to prevent injury tonearby areas including anywhere along the endoscopic path, the region asdefined by placement of the catheter shaft 104. For exemplary purposes,and not limitation, endoscopic paths may include passageways through theesophagus, stomach, endoscope or endoscopic lumen, visualizationapparatus (e.g. EUS), or paths created by a physician's hand. As shownin FIGS. 2 and 3, the catheter shaft 104, outer sheath 103, and handle105 include heating or defrosting elements 112 (as indicated by the hashmarks) that prevent the shaft from freezing to an endoscope. The heatingelements 112 comprise one or more electrically conductive wiresintegrated within the catheter shaft, sheath, and handle but may alsoinclude a mesh of heating wire to promote a more uniform heatdistribution. Any configuration of wires may be utilized including, butnot limited to, linear configurations, spiral arrangements of wires, ormesh formations. The heating elements 112 apply mild heat adjacentstructures to prevent freezing, such as to prevent freezing between thecatheter shaft 104 and the sheath 103, as well as between the cathetershaft 104 and tissue along the endoscopic path. The heating elements 112reduce, and preferably eliminate, risk of damage to non-target tissueareas as well as to an independently operated endoscope.

For exemplary purposes only, and not limitation, the endoscopiccryocatheter or the independently operated endoscope may integrate anoptical visualization tool, an ultrasound device, magnetic resonanceimaging (MRI), computed tomography (CT), or any other visualizationtechnique, alone or in combination, and with any compatible tool ortechnique.

Referring to FIGS. 2 and 3, the endoscopic cryocatheter 100 is insulatedalong the length of the shaft 104. This insulation is achieved by aninsulative vacuum lumen 126 within the catheter shaft 104 upon which avacuum is drawn. In FIG. 2, the probe tip 102 is covered by the sheath103 (protracted configuration) when the handle is moved toward thedistal end of the apparatus 100 (movement as indicated by the arrows).The probe tip and catheter are encased in the sheath 103 which coversthe probe tip during catheter insertion to prevent damage to theendoscope, endoscopic cryocatheter 100, or puncture of tissue duringendoscopic placement of the endoscopic cryocatheter 100 to an internaltreatment site. In FIG. 3, the probe tip 102 is exposed when the handle105 is moved towards the proximal end allowing the sheath 103 to retractat a tissue site designated for treatment. Additionally, any catheter orprobe tip or configuration (needle, paddle, etc.) can be utilized anddetachably affixed as long as it passes through the dimensions of thecatheter shaft 104. When positioned to a treatment site through anendoscope (not illustrated), the sheath 103 is retracted to expose theablation probe tip 102.

One embodiment of the probe tip 102 is illustrated as a needle-tip probe102 capable of piercing a tissue. In one aspect, the needle-tip probe102 is a sharp-pointed and stiff needle to penetrate the stomach walland/or pancreatic parenchyma. The needle-tip probe 102 comprises anablation zone, or freeze zone 122 at a far distal portion of the probetip. The needle-tip probe 102 may be about 1.5 mm in diameter by about 4cm, or may be up to about 15 cm in length, and may have an ablation zoneof between about 10 mm-20 mm, or up to about 40 cm or longer. In someembodiments, the ablation zone may be about 12 mm to about 15 mm inlength, dependent on the size of the needle tip probe. Any size, shapeand dimension of needle can be utilized, as desired, depending on thetissue to be ablated. In addition, the probe tip 102 is compatible witha liquid or gas cryogen, or any cryogenic fluid, and allows theformation of ice at a tissue site. As such, the needle probe tip 102 issecurely affixed to an internal wall of the catheter shaft 104 by athermo-compatible adhesive. Thermal elements 146 in the probe tip 102allow for thaw of the frozen tissue and release of the probe tip fromthe treated tissue (See depiction in FIGS. 2 and 3). The thermalelements 146 also act as spacers to maintain distance between thecatheter shaft 104 and the supply and return lines. As illustrated here,the ablation zone 122 extends forward from the thermal elements 146 tothe distal-most portion of the probe tip 102. Without limitation, theablation zone may be created within any portion of the probe tip tointegrate various portions, sizes, and dimensions as desired.

In another aspect, the sharp needle-like probe tip is capable ofpenetrating any desmoplasia, fibrous connective tissue, tumorinfiltrate, and scar or fibrosis. Additionally, the sharpness of theneedle-like probe tip can be used for EUS guided pseudocyst drainageduring a procedure. The EUS cryoablation procedure provides surgeonswith a minimally invasive tool that reduces morbidity and lowers costs.

In yet another aspect, the probe tip may be a blunt probe or cathetertip that forms an ablation zone at a focal point or along a linear path.Various embodiments of a probe tip may be incorporated herein withoutlimitation.

One embodiment utilizes a catheter shaft 104 that interconnects with theprobe tip 102 to provide continuous cryofluid delivery and return fromthe cryo-system. The connector 113 enables cryogen to run from thecryo-source at the proximal end of the apparatus 100 to the probe tip102 at the distal end.

As depicted in FIGS. 4A and 4B, a distal end of an endoscopiccryoablation catheter 400 is magnified. A needle-tip probe 402 with anablation zone 422 is connected to a catheter shaft 404 by way of anadhesive 444. Within the catheter shaft 404 is a supply line 406defining a cryogen supply lumen 416 that runs longitudinally the lengthof the apparatus 400 and extends to a cryogen source at the console. Thecryogen return line 408 circumferentially encases the supply line 406such that a return lumen 418 is formed therebetween. Spacers 446 at thedistal end of the needle-tip probe 402 maintain a space between thereturn line 408 and an inner surface 448 of the needle-tip probe. Thesupply line 406 and return line 408 run the length of the apparatus 400(as similar to the invention as shown in FIG. 1). The coaxial design ofcryogen supply line within the return line allows for more efficient useof space inside the catheter as compared to a side by side supply-returnline design. Thus, the coaxial design provides catheter shafts havingsizes as small as 0.5 mm or smaller; and catheter shafts can bemanufactured up to about 1 cm or greater. In one aspect, the cathetershafts and probes can be interchanged depending on designated use inminimally invasive treatments and surgical, respectively. The cathetershaft 404 also creates an insulating lumen 423 to which an active orpassive insulation can be applied. Active insulation is created when avacuum is applied within the insulating lumen 423, or when heat isapplied. Passive insulation allows gaseous components to occupy theinsulating lumen 423, or where foam and other insulative materials areconfigured therein. See FIG. 4C which depicts a cut-away cross-sectionof FIG. 4A.

In the embodiment of the apparatus 400, as depicted in FIGS. 4A, 4B, and4C, a thermal insulation 426 is utilized in both the catheter shaft 404and the sheath 403. The thermal insulation 426 depicted includes aninsulative thermoelectric mesh that integrates a plurality of electricalwires. The wire mesh uniformly insulates the catheter and sheath fromcryogenic temperatures. The heat applied to the catheter shaft 404 andto the sheath 403 prevents freezing of the catheter and sheath whileprotecting endoscopic walls and cryocatheter components, and shieldingtissues that are not designated for treatment. In another aspect, thethermal insulation may include one or more thermo-electric resistancewires in a linear arrangement, spiral, or mesh configuration.

As depicted in FIGS. 4A, 4B, and 4C, several electrical and mechanicaldeflection wires 427 are integrated within an internal wall of thecatheter shaft 404 and sheath 403 to move and steer the distal end atthe probe tip 402. In one aspect, the sheath is the steerable portionthat integrates deflection wires 427 and directs the probe tip to thetissue site. In another aspect, the catheter shaft integrates thedeflection wires 427 that direct the distal end to the tissue site.Deflection wires may be integrated along any wall of the longitudinallength of the apparatus and controlled via the handle controls or at amain console.

In one aspect, an accessory injection tube 449 is positioned within theinsulating lumen 423 and extends longitudinally along the catheter shaft404. The accessory injection tube 449 emerges at the distal end of aneedle tip 402 at an exit portal 447. The accessory injection tube 449allows for the introduction of drugs and therapeutic agents such aschemotherapeutic agents, gene therapy vectors and agents, hormones,vitamins, pro-apoptotic or anti-apoptotic agents, and clotting agents,for exemplary purposes and not limitation. The drugs and therapeuticagents can be introduced prior to, during and/or following an ablationprocedure. Tissues and aspirate may also be withdrawn through theaccessory tube 449.

An embodiment of the invention as shown in FIG. 5 illustrates a sectionof an endoscopic ablation catheter apparatus 500. Depicted is anumbilical 510 attached to a retraction guide 509. At an opposite end, aflexible catheter 504 is affixed to the retraction guide by adhesives513 comprised of epoxy or cyanoacrylate adhesives, or other medicalgrade superglue. A handle 505 attaches to an outer sheath 503 at adistal end of the apparatus 500 such that the outer sheath 503 can bemoved in the x-y directional axis as desired by the user. The handle 505surrounds the catheter 504 and retraction guide 509 to form anintegrated handheld portion 511. The handheld portion 511 alsoincorporates heating elements 520 to protect the user fromcryo-temperatures generated within the device. As illustrated here, aninternal forward stop 522 allows the handle 505 and sheath 503 to moveback, synchronously, a pre-determined distance such that the handlecovers a portion of the retraction guide 509. A reverse stop 523 of theretraction guide 509 allows the handle 505 and sheath 503 to be pushedforward a pre-determined distance over the catheter shaft 504. Distancescan be indicated at 0.5 cm markings on the handle portion 511 toallocate the desired protraction and retraction of the sheath. Anydesired increment, however, may be designated and marked. The markingsallow the user to customize movement of the outer sheath 503 to adesirable location and keep record of the length of catheter shaft orprobe tip exposed. Additionally, in some embodiments the sheath may bethe limiting factor so as to designate the distance the handle ispermitted to retract in which the sheath is not permitted to move beyondthe larger diameter of the retraction guide.

As illustrated, a supply line 506 has an internal lumen 516 for deliveryof cryogenic fluid to a probe tip. Return line 508 is positioned aboutthe supply line to form a cylindrical lumen 518 disposed longitudinallywith the supply line 506 throughout the length of the endoscopiccryoablation apparatus. Further, on/off controls 533 and 534 provideelectrical connection 544 and 545, respectively, to allow the user toturn on/off the cryogen source, thaw, and/or heating elements 520. Othercontrols may be implemented to control gaseous discharge from thecryo-return lines, heating mechanisms throughout the length of theapparatus, temperatures adjustments, thermal monitoring, andvisualization, among others. Automated operation of the apparatus mayalso be incorporated with the use of software based systems. In oneaspect, automated control mechanisms also operate the sheath,individually or in combination with the handle. Further, the controls ofthe invention can be motorized for gradual precise positioning, as wellas computerized to operate protraction and retraction of the sheath insynchrony with the handle. Any number of components of the invention maybe motorized, computerized, and programmed as desired. Where theendoscopic cryocatheter is programmed, specific patient parameters maybe integrated with a software program to facilitate placement of theprobe tip, temperature adjustments, and treatment durations.

In another aspect, as shown in FIG. 5, the endoscopic cryoablationcatheter 500 comprises an injection channel 555, access port 556, andaccessory tube 557 for administering drugs, adjuvants, and therapeuticagents at the target tissue site. The access port 556 is a rigid twistlock within the handheld portion 511, but may also be a flexible tube toallow introduction of an agent via a syringe or similar mechanism. Theaccess port 556 is positioned on an outer wall 519 of the retractionguide 509 but may be positioned anywhere in the handle portion 511 oralong the length of the umbilical 510 or catheter shaft 504. Theinjection channel 555 allows entry of the agent into the accessory tube557; the accessory tube 557 then runs longitudinally the length of thecatheter shaft 504 to the distal end at the probe tip. An exit portal(not depicted here) within the needle tip seals a terminal portion ofthe accessory tube 557 to the needle tip to prevent any cryogen leakingfrom the needle tip probe. The accessory tube 557 is configured adjacentto the return line 508, within or along the catheter shaft 504 to allowfor the introduction of additional adjuvants and agents as used intherapies such as chemotherapy, gene therapy, hormone and vitamintherapies. Such agents may include chemotherapeutic agents, gene therapyvectors, hormones, vitamins, pro-apoptotic or anti-apoptotic agents, andclotting agents, among others. The agents may be introduced at any stageof the procedure, including before, during, or after an ablationprocedure. This accessory channel 557, along with the injection channel555 and access port 556 can also be utilized for the introduction ofbiopsy needle apparatus, aspiration of fluid or tissue, or other deviceas desired. Additionally, the introduction of other ablative devicessuch as RF, high frequency ultrasound (HiFU), laser, or other ablativeenergies can be introduced. These channels within or along theendoscopic cryocatheter allow for the application of multiple treatmentmodalities to more effectively destroy the target tissue.

Further, in another aspect, the flexible endoscopic catheter of theinvention may integrate any ablative device within the internal lumen ofthe catheter so as to advantageously allow for a plurality of treatmentmodalities through an integral tube. The consolidation of ablationdevices minimizes invasiveness in patient treatment as well as treatmenttimes and duration of the overall procedure.

In one embodiment, the catheter assembly, including supply and returnlines encompassed in a catheter shaft, is contained in a sheath whichslides freely over the outer surface of the catheter shaft allowing forthe covering and uncovering of the probe tip during insertion andretraction of the endoscopic cryocatheter. In another embodiment, aportion of the catheter assembly is positioned over the freely slidingsheath. The sheath may comprise an insulative heating element along aportion or entire length of the catheter shaft to prevent freezingbetween the cryocatheter assembly and a wall of an endoscope. Anyportion of the catheter shaft or the entire shaft can include theheating elements or insulative materials. The sheath terminates at thehandle of the cryocatheter assembly and is affixed to the handle whereinmovement of the handle and sheath sub-assembly causes movement of thesheath forward and backward to cover or uncover the probe tip,respectively. The components may be individually attached and affixedvia adhesive or injection molded to form an integral component, orintegral handle and sheath sub-assembly. The cryogen supply and returnlines continue through the handle and through the umbilical to theconnector where the coaxial lines diverge into independent cryogensupply and return lines. The connector compatibly aligns and seals witha connection of a cryogen source console.

In addition, between the cryogen return line and the umbilical is alumen in which a vacuum or other type of insulation can be applied. Thisprovides additional insulation to prevent freezing between components ofthe apparatus. Within or along the umbilical, control lines andelectrical wires to control thawing, thermal monitoring, sheathmovement, catheter tip steering, and accessory channels may becontained. The lines may run in a secondary umbilical parallel to thatof the cryogen lines if so desired. This configuration separates theelectromechanical control lines from that of the cryolines, whileproviding a reduced overall device size and footprint.

B. Cryoablation Catheters without a Sheath

Turning to FIGS. 6-14, these figures illustrate various embodiments inwhich, in contrast with the foregoing embodiments, needle-tip probe 602is affixed at joint 650 to the distal end of return line 608 withincatheter shaft 604. Joint 650 may use adhesive such as, e.g., glue, toadhere needle tip probe 602 to return line 608. In these embodiments,needle-tip probe 602 is axially moveable in relation to the surroundingcatheter shaft 604. Catheter shaft 604 may also be rotationally movablearound needle-tip probe 602 and return line 608.

Aside from the absence of the sheath, and differences in actuation ofneedle probe tip 602 with respect to catheter shaft 604, device 600 ofFIGS. 6-14 operates substantially similarly to devices 100/400/500 ofFIGS. 1-5, respectively. Specifically, any feature described above withrespect to device 100/400/500 may also be combined with device 600. Anysuch combinations are omitted only in the interest of brevity.

As best shown in FIG. 8, the device 600 includes a catheter shaft 604.Within catheter shaft 604, a cryogen supply line 606 is provided, havinga lumen 616 therein. Cryogen supply line 606 may be substantiallyconcentrically surrounded within catheter shaft 604 by a cryogen returnline 608 having a lumen 618 therein, such that cryogen supply line 606is disposed within cryogen return lumen 618. Cryogen return line 608 isdisposed within catheter shaft 604, again in a substantially concentricarrangement. The cross sectional diameter of catheter shaft 604 issubstantially greater than the cross sectional diameter of return line608, leaving a gap circumferentially surrounding return line 608 withincatheter shaft 604. This gap, between the inner wall of the catheter 604and the outer wall of the return line 608, serves as insulating lumen623, which provides thermal insulation to return line 608. Insulatinglumen 423 is similar in structure and function to insulating lumen 423(FIG. 4C).

As shown in FIG. 8, device 600 may also include an accessory injectiontube 649, running substantially parallel to return line 608, supply line606, and catheter shaft 604. Accessory injection tube 649 may bedisposed within insulating lumen 623, such that it is within cathetershaft 604 but outside of return line 608. As shown in, e.g., FIGS. 6-7,accessory injection tube 649 may run the length of the device and mayterminate at a distal end at an exit portal 647 in needle tip probe 602.Accessory injection tube 649 and exit portal 647 may be used incombination to deliver various treatment agents, e.g., anticanceragents, in conjunction with (i.e., any one or more of before, during, orafter) an ablation procedure. Accessory injection tube 649 is similar instructure and function to the accessory injection tubes 449 (FIGS. 4A-B)and 557 (FIG. 5), and exit portal 647 is similar in structure andfunction to exit portal 447 (FIGS. 4A-B).

As previously described, device 600 includes a cryogen supply line 606,which supplies liquid cryogen to the distal tip of needle tip probe 602.As shown in, e.g., FIGS. 6-7, cryogen supply line 606 extends in adistal direction further than return line 608, such that supply line 606extends distally further into needle tip probe 602 than itsconcentrically surrounding return line 608. Liquid or gas form cryogenis supplied through supply line 606 to needle probe tip 602, where itcontacts inner surface 648 of needle probe tip 602. Heat exchange occursacross the surface of needle probe tip 602 between the cryogen withinneedle probe tip 602 and the target tissue, resulting in cryoablation,or tissue destruction, of tissue in contact with the ablation zone 622of needle probe tip 602. Cryogen is then removed from needle tip probe602 via return line 608.

The devices of FIGS. 6-14 are designed to be compatible with a number ofcryogens, operating temperatures, and pressures. For exemplary proposesthese cryogens may include argon, carbon dioxide, nitrous oxide,nitrogen gas, liquid nitrogen, pressurized and mixed phase cryogens,dual phase cryogens, propane, critical and super critical nitrogen, andothers. Cryogen input operating pressures can range from about 50 psi toabout 10,000 psi, and more commonly from about 1,000 psi to about 4,000psi. Depending on the procedure and other parameters, cryogen operatingtemperatures within the needle tip probe 602 may typically range fromabout −70° C. to about −210° C. during operation, once cryogen flow tothe ablation zone 622 has stabilized during operation. Various devicesand methods for supplying cryogen to device 600 may be used, such as,e.g., those described in U.S. Pat. No. 9,089,316 and U.S. applicationSer. No. 14/687,449, which are incorporated by reference herein asthough fully set forth.

For delivery and return of the cryogen to the ablation zone 622 at thetip of the needle tip probe 602, a series of cryogen supply:returnvolume (e.g. cross sectional area of the tubing) ratios can be used in acoaxial configuration to provide optimal flow and heat extraction ratesin the ablation zone 622 while minimizing choking flow created by backpressure. For example, the supply:return volume ratio may range from1:1, 1:1.5; 1:2; or greater. As an example, the inner diameter of supplyline 606 may be between about 0.33 mm and 1.5 mm, and the inner diameterof return line 608 may be between about 0.63 mm to 4.5 mm Determinationof the desired supply:return volume ratio must include accounting forthe internal diameter and the outer diameter (wall thickness) of thesupply line 606 in relation to the inner diameter of the return line608. This 1:1 or greater supply to return ratio (cross sectional areaand/or volume) applies similarly to the ablation zone 622 within theprobe tip 602.

Catheter shaft 604 itself, shown in cross section in FIG. 8, may be madeof a flexible polymer material, and may range in diameter from, e.g.,about 2 mm to about 10 mm, and in length from about 0.5 m to about 1.5m. For example, an illustrative catheter shaft 604 may have a diameterof 3 mm and a length of 1 m, although larger and smaller diameters arealso contemplated. In various embodiments, device 600 may furtherinclude deflection wires 627 embedded within the wall of catheter shaft604 (as shown in FIG. 8) or adjacent the walls of catheter shaft 604,for use in directing and steering the needle probe tip 602 during use.Deflection wires 627 are similar in structure and function to deflectionwires 427 (FIGS. 4A-C). The catheter shaft 604 may also include heatingelements 626, which may also be embedded within the walls of cathetershaft 604. Heating elements 626 may be, e.g., resistance wires or otherthermal insulation components to prevent unwanted freezing alongcatheter shaft 604. Heating elements 626 are similar in structure andfunction to heating elements 426 (FIGS. 4A-C).

As shown in the embodiments of FIGS. 6-7, the needle-tip probe 602 maybe affixed at joint 650 to the outer wall of return line 608. In otherembodiments, as shown in FIGS. 9-10, the needle-tip probe 602 may beaffixed at joint 650 to the inner wall of the return line 608.Regardless of whether needle-tip probe 602 is affixed to the inner wallor outer wall of return line 608, when device 600 is in the extendedposition as shown in FIGS. 6 and 9, the catheter shaft 604 is in theforward position and covers the distal tip of the needle-tip probe 602.When in the retracted position (as illustrated in FIGS. 7 and 10), thecatheter shaft 604 is retracted and the distal tip of the needle tipprobe 602 is exposed (FIGS. 7 & 10).

As shown in FIGS. 11-14, in some embodiments, return line 608 may becontained within an insulating tube 660. In these embodiments, tube 660may be disposed within the catheter shaft 604 such that it substantiallyconcentrically surrounds return line 608. Tube 660 may be thermallyinsulated using any form of insulation such as, e.g., vacuum insulation.Tube 660 may be affixed to needle probe tip 602 at joint 650, so thatits position is substantially fixed with respect to return line 608, butcatheter shaft 604 may freely move in an axial and/or rotationaldirection around tube 660 as shown in FIGS. 11-12.

In some embodiments, as shown in FIGS. 13-14, needle probe tip 602 mayalso include insulation 662 thereon. Insulation 662 may either be anintegrally formed with needle probe tip 602, or may be a separate memberapplied over the proximal end of needle tip probe 602, such as a band ofinsulation that concentrically surround the proximal end of needle tipprobe 602. In embodiments in which insulation 662 is applied over theproximal end of needle tip probe 602, it may be affixed at joint 663via, e.g., epoxy, glue, solder, welding, brazing or any other methodsuitable for securing the insulation 662 to needle tip probe 602, aswill be appreciated by one of skill in the art. In either event, a lumen664 is provided within insulation 662, through which supply line 606extends distally. Insulation 662 may be about 1 cm to about 20 cm inlength, depending on the dimensions of needle tip probe 602. At thedistal end of the insulation 662, needle tip probe 602 includes noinsulation. This distal, uninsulated portion of needle tip probe 602 isthe ablation zone 622.

The combination of the proximal portion of needle tip probe 602 thatincludes insulation 662, and the uninsulated distal end of needle tipprobe 602 that forms ablation zone 622, restricts tissue freezing to thedistal tip of needle tip probe 602. Insulation 662 prevents freezedamage to tissue adjacent to the proximal end of needle tip probe 602.This allows insertion of the ablation zone 622 into, and destruction oftissue targets anywhere within a tissue or organ without damagingnon-targeted tissues adjacent to the insulation 662.

Insulation 662 may be any of a number of types of thermal insulationincluding but not limited to a permanent vacuum sleeve, drawing of anactive vacuum, an air gap lumen, low thermal capacity material, a gaslumen, and active thermoelectric heating. In various embodiments, any ofthe forgoing types of thermal insulation may be used to provideinsulation for catheter shaft 604 (FIGS. 6-14) and/or insulating tube660 (FIGS. 11-14) in addition to insulation 662.

C. Cryoablation Catheter with Insulated Catheter Shaft

Turning to FIG. 15, an embodiment of the invention as shown illustratesa section of the endoscopic ablation catheter apparatus 700. Depicted isthe umbilical 710 attached to the retraction guide 709. Within theretraction guide, flexible return line 708 is affixed to the proximaland/or distal ends of the retraction guide 709 within the handle 705 byadhesives 713. Adhesives 713 may be epoxy, cyanoacrylate adhesives, orother medical grade superglue. The handle 705 attaches to a cathetershaft 704 at a distal end of the apparatus 700 such that the return line708 can be moved in the x-y direction along the longitudinal axis inrelation to the catheter 704 as desired by the user. The handle 705surrounds the catheter 704 and retraction guide 709 to form anintegrated handheld portion 711. The handheld portion 711 may alsoincorporate heating elements 720 to protect the user fromcryo-temperatures generated within the device. As illustrated here, aninternal forward stop 722 allows the handle 705, catheter 704 and returnline 708 to move back and forth along the longitudinal axis,synchronously, a pre-determined distance such that the handle covers aportion of the retraction guide 709. A reverse stop 723 of theretraction guide 709 allows the handle 705, catheter 704 and return line708 to be pushed forward (i.e., distally) a pre-determined distancethereby causing the distal end of the return line 708 and probe tip (notpictured) to emerge from the distal end of the catheter 704 (not shown).Distances can be indicated at, e.g., 0.5 cm markings on the handleportion 711 to allocate the desired protraction and retraction of thereturn line 708 in relation to the catheter 704. Any desired increment,however, may be designated and marked, e.g., centimeters, millimeters,fractions of an inch, etc. The markings allow the user to customizemovement of the return line 708 to a desirable location thereby allowinga record of the length of return line or probe tip exposed.Additionally, in some embodiments the return line may be the limitingfactor so as to designate the distance the handle is permitted toretract in which the return line is not permitted to move beyond thelarger diameter of the retraction guide. Additionally in someembodiments, the handheld portion 711 may also include a reinforcementtube 760. Reinforcement tube 760 is affixed on an inner surface thereofto the outer surface of the return line 708. Reinforcement tube 760 mayalso be affixed on the outer surface thereof to the inner surface of theretraction guide 709 (not shown). The reinforcement tube 760 may becontained within and may protrude at either or both the distal orproximal end from the retraction guide 709. This reinforcement tube 760may provide additional support to the return line 708 during actuationof the handheld portion 711.

As illustrated, the supply line 706 has the internal lumen 716 fordelivery of cryogenic fluid to the probe tip. Return line 708 ispositioned circumferentially about the supply line 706 to form thecylindrical lumen 718 disposed longitudinally within the supply line 706throughout the length of the endoscopic cryoablation apparatus. Further,on/off controls 733 and 734 provide electrical connection 744 and 745,respectively, to allow the user to turn on/off the cryogen source, thaw,and/or heating elements 720. Other controls may be implemented tocontrol gaseous discharge from the cryo-return lines, heating mechanismsthroughout the length of the apparatus, temperatures adjustments,thermal monitoring, and visualization, among other features. Automatedoperation of the apparatus may also be incorporated with the use ofsoftware-based systems. In one aspect, automated control mechanisms alsooperate the sheath, individually or in combination with the handle.Further, the controls of the invention can be motorized for gradualprecise positioning, as well as computerized to operate protraction andretraction of the sheath in synchrony with the handle. Any number ofcomponents of the invention may be motorized, computerized, andprogrammed as desired. Where the endoscopic cryocatheter is programmed,specific patient parameters may be integrated with a software program tofacilitate placement of the probe tip, temperature adjustments, andtreatment durations.

In another aspect, as shown in FIG. 15, the endoscopic cryoablationcatheter 700 may also comprise an injection channel 755, access port756, and accessory tube 757 for administering drugs, adjuvants, andtherapeutic agents at the target tissue site. The access port 756 may bea rigid twist lock within the handheld portion 711, but may also be aflexible tube to allow introduction of an agent via a syringe or similarmechanism. The access port 756 may be positioned on the outer wall 719of the retraction guide 709, or anywhere in the handle portion 711 oralong the length of the umbilical 710 or catheter shaft 704. Theinjection channel 755 allows entry of the agent into the accessory tube757; the accessory tube 757 then runs longitudinally along the length ofthe catheter shaft 704 to the distal end at the probe tip. An exitportal (not depicted here) within the probe tip seals a terminal portionof the accessory tube 757 to the probe tip to prevent any cryogenleaking from the probe tip. The accessory tube 757 is configuredadjacent to the return line 708, within or along the catheter shaft 704to allow for the introduction of additional adjuvants and agents as usedin therapies such as chemotherapy, gene therapy, hormone and vitamintherapies. Such agents may include chemotherapeutic agents, gene therapyvectors, hormones, vitamins, pro-apoptotic or anti-apoptotic agents, andclotting agents, among others. The agents may be introduced at any stageof the procedure, including before, during, or after an ablationprocedure. This accessory channel 757, along with the injection channel755 and access port 756 can also be utilized for the introduction ofbiopsy needle apparatus, aspiration of fluid or tissue, or other deviceas desired. Additionally, the introduction of other ablative devicessuch as RF, high frequency ultrasound (HiFU), laser, or other ablativeenergies can be introduced. These channels within or along theendoscopic cryocatheter allow for the application of multiple treatmentmodalities to more effectively destroy the target tissue.

Turning to FIGS. 16-24, these figures illustrate various embodiments inwhich, in contrast with the foregoing embodiments, needle-tip probe 802is affixed at joint 850 to the distal end of return line 808 withincatheter shaft 804. Joint 850 may use adhesive such as, e.g., glue, toadhere needle tip probe 802 to return line 808. Within the cathetershaft there is an insulative tube 870 which is affixed to catheter shaft804 at the distal end of the catheter shaft 804 at joint 871. A similarjoint 871 may also affix the catheter 804 to the insulative tube 870 atthe proximal end of the catheter shaft (not shown). As illustrated incross section in FIG. 20, the circumferential space between the cathetershaft 804 and insulative tube 870 creates an insulative lumen 872 alongthe length of the catheter 804 thereby creating an insulated cathetershaft. The insulative tube 870 is fixed in its axial position inrelation to the catheter 804. The insulation in the insulative lumen 872may include, but is not limited to, a permanent vacuum sleeve, drawingof an active vacuum, an air gap lumen, low thermal capacity material, agas lumen, and active thermoelectric heating.

In these embodiments, needle-tip probe 802 is axially moveable inrelation to the surrounding catheter shaft 804, insulative tube 870, andinsulative lumen 872. Catheter shaft 804, insulative tube 870 andinsulative lumen 872 may also be rotationally movable around needle-tipprobe 802 and return line 808.

Aside from the absence of the sheath and the inclusion of the insulativetube 870 and insulative lumen 872, and differences in actuation ofneedle probe tip 802 and return line 808 with respect to catheter shaft804, device 800 of FIGS. 16-24 operates substantially similarly todevices 100/400/500/600 of FIGS. 1-14, respectively. Specifically, anyfeature described above with respect to device 100/400/500/600 may alsobe combined with device 700 of FIG. 15 and device 800 of FIGS. 16-24.Any such combinations are omitted only in the interest of brevity.

As best shown in FIG. 16, the device 800 includes catheter shaft 804.Within catheter shaft 804, cryogen supply line 806 is provided, havinglumen 816 therein. Cryogen supply line 806 may be substantiallycircumferentially, e.g., concentrically surrounded within catheter shaft804 by cryogen return line 808 having lumen 818 therein, such thatcryogen supply line 806 is disposed within cryogen return lumen 818.Cryogen return line 808 is disposed within insulative tube 870 which isdisposed within catheter shaft 804, again in a circumferential, e.g.,substantially concentric arrangement. The cross sectional inner diameterof catheter shaft 804 is substantially greater than the cross sectionalouter diameter of insulative tube 870 leaving a gap circumferentiallysurrounding insulative tube 870 within catheter shaft 804. The gapbetween the inner wall of the catheter 804 and the outer wall of theinsulative tube 870 creates an insulative lumen 872, which providesthermal insulation to return line 808. Insulative lumen 872 is similarin structure and function to insulating lumen 423 (FIG. 4C) and 623(FIGS. 6-14). The cross sectional diameter of insulative tube 870 isgreater than the cross sectional outer diameter of return line 808,leaving a gap circumferentially surrounding return line 808 withininsulative tube 870 thereby allowing the return line 808 to move freelywithin the insulative tube 870.

FIG. 16 illustrates the needle-tip probe 802 and return tube 808 in aretracted position within the catheter 804 and insulative tube 870,whereas FIG. 17 illustrates the needle-tip probe 802 and return line 808in an extended position, in which the needle tip probe 802 and returnline 808 extend distally out of the catheter 804 and insulative tube870. The distance the needle-tip probe can extend beyond the distal endof catheter 804 varies and can be determined by a user through actuationof the handle mechanism as described relative to FIGS. 5 and 15.

As shown in FIG. 18, device 800 may also include an accessory injectiontube 849, running substantially parallel to return line 808, supply line806, insulative tube 870 and catheter shaft 804. Accessory injectiontube 849 may be disposed within insulative lumen 872, such that it iswithin catheter shaft 804 but outside of insulative tube 870.Alternatively, the accessory injection tube 849 may be disposed withinthe insulative tube 870 but outside the return line 808. As shown in,e.g., FIGS. 18-19, accessory injection tube 849 may run the length ofthe device and may terminate at a distal end at an exit portal 847 inneedle tip probe 802. The accessory injection tube 849 may also run thelength of the device and may terminate at a distal end at an exit portalat the distal end of the catheter 804 (not shown). Accessory injectiontube 849 and exit portal 847 may be used in combination to delivervarious treatment agents, e.g., anticancer agents, in conjunction with(i.e., any one or more of before, during, or after) an ablationprocedure. Accessory injection tube 849 is analogous in structure andfunction to the accessory injection tubes 449 (FIGS. 4A-B), 557 (FIG. 5)and 649 (FIGS. 6-7 and 11-14), and exit portal 847 is analogous instructure and function to exit portal 447 (FIGS. 4A-B) and 647 (FIGS.6-7 and 11-14).

As previously described, device 800 includes a cryogen supply line 806,which supplies liquid cryogen to the distal tip of needle tip probe 802.As shown in, e.g., FIGS. 16-17, cryogen supply line 806 extends in adistal direction further than return line 808, such that supply line 806extends distally further into needle tip probe 802 than itscircumferentially surrounding return line 808. Liquid or gas formcryogen is supplied through supply line 806 to needle probe tip 802,where it contacts inner surface 848 of needle probe tip 802. Heatexchange occurs across the surface of needle probe tip 802 between thecryogen within needle probe tip 802 and the target tissue, resulting incryoablation, or tissue destruction, of tissue in contact with theablation zone 822 of needle probe tip 802. Cryogen is then removed fromneedle tip probe 802 via return line 808.

The devices of FIGS. 16-24 are designed to be compatible with a numberof cryogens, operating temperatures, and pressures. For exemplaryproposes these cryogens may include argon, carbon dioxide, nitrousoxide, nitrogen gas, liquid nitrogen, pressurized and mixed phasecryogens, dual phase cryogens, propane, critical and super criticalnitrogen, and others. Cryogen input operating pressures can range fromabout 50 psi to about 10,000 psi, and more commonly from about 1,000 psito about 4,000 psi. Depending on the procedure and other parameters,cryogen operating temperatures within the needle tip probe 802 maytypically range from about −70° C. to about −210° C. during operation,once cryogen flow to the ablation zone 822 has stabilized duringoperation. Various devices and methods for supplying cryogen to device800 may be used, such as, e.g., those described in U.S. Pat. Nos.9,089,316 and 10,054,262, which are incorporated by reference herein asthough fully set forth.

For delivery and return of the cryogen to the ablation zone 822 at thetip of the needle tip probe 802, a series of ratios of cryogensupply:return volume (e.g. cross sectional area of the tubing) can beused in a coaxial configuration to provide optimal flow and heatextraction rates in the ablation zone 822 while minimizing choking flowcreated by back pressure. For example, the supply:return volume ratiomay range from 1:1, 1:1.5; 1:2; or greater. As an example, the innerdiameter of supply line 806 may be between about 0.33 mm and 1.5 mm, andthe inner diameter of return line 808 may be between about 0.63 mm to4.5 mm Determination of the desired supply:return volume ratio mustinclude accounting for the internal diameter and the outer diameter(wall thickness) of the supply line 806 in relation to the innerdiameter of the return line 808. This 1:1 or greater supply to returnratio (cross sectional area and/or volume) applies similarly to theablation zone 822 within the probe tip 802.

Catheter shaft 804 itself, shown in cross section in FIG. 20, may bemade of a flexible polymer material, and may range in diameter from,e.g., about 2 mm to about 10 mm, and in length from about 0.5 m to about1.5 m. For example, an illustrative catheter shaft 804 may have adiameter of 3 mm and a length of 1 m, although larger and smallerdiameters are also contemplated. In various embodiments, device 800 mayfurther include deflection wires 827 embedded within the wall ofcatheter shaft 804 (as shown in FIG. 20) or adjacent the walls ofcatheter shaft 804, for use in directing and steering the needle probetip 802 during use. Deflection wires 827 (FIGS. 16-24) are analogous instructure and function to deflection wires 427 (FIGS. 4A-C) and 627(FIGS. 6-14). The catheter shaft 804 may also include heating elements826, which may also be embedded within the walls of catheter shaft 804.Heating elements 826 may be, e.g., resistance wires or other thermalinsulation components to prevent unwanted freezing along catheter shaft804. Heating elements 826 are analogous in structure and function toheating elements 426 (FIGS. 4A-C) and 626 (FIGS. 6-14). The cathetershaft may also contain an insulative tube 870 between the inner wall ofthe catheter 804 and the outer wall of the return line 808 creating ainsulative lumen 872.

As shown in the embodiments of FIGS. 16 and 17, the needle-tip probe 802may be affixed at joint 850 to the outer wall of return line 808 as inFIGS. 11-12, joint 650. In other embodiments, similar to the mannershown in FIGS. 9 and 10, the needle-tip probe 802 may be affixed atjoint 850 to the inner wall of the return line 808. Regardless ofwhether needle-tip probe 802 is affixed to the inner wall or outer wallof return line 808, when device 800 is in the catheter extended positionas shown in FIGS. 16 and 18, analogous to FIGS. 6, 9, 11 and 13, thecatheter shaft 804 is in the forward position and covers the distal tipof the needle-tip probe 802. When in the retracted position (asillustrated in FIGS. 17 and 19, and analogous to FIGS. 7, 10 and 14),the catheter shaft 804 is retracted and the distal tip of the needle tipprobe 802 is extended beyond the end of the catheter 804. (FIGS. 17 and19). Extension of the needle-tip probe 802 beyond the distal end of thecatheter 804 may be accomplished by either retraction of the catheter804 or extension of the return line 808 and needle-tip probe 802 inrelation to one another.

As shown in FIGS. 16-24, in some embodiments, return line 808 may becontained within an insulative tube 870. In these embodiments, theinsulative tube 870 may be disposed within the catheter shaft 804 suchthat it circumferentially, e.g., substantially concentrically surroundsreturn line 808. Insulative tube 870 may be thermally insulated usingany form of insulation including but not limited to a permanent vacuumsleeve, drawing of an active vacuum, an air gap lumen, low thermalcapacity material, a gas lumen, and active thermoelectric heating.Insulative tube 870 may be affixed to the inner wall of the catheter 804at joint 871, so that its axial position is substantially fixed withrespect to catheter 804, but catheter shaft 804 and insulative tube 870may freely move in an axial and/or rotational direction in relation tothe return line 808 and needle tip 802 as shown in FIGS. 16-24.

In some embodiments, as shown in FIGS. 21-24, needle probe tip 802 mayalso include insulation 862 thereon. Insulation 862 may either beintegrally formed with needle probe tip 802, or may be a separate memberapplied over or within the proximal end of needle tip probe 802, such asa band of insulation that concentrically surrounds or is disposed withinthe proximal end of needle tip probe 802. In embodiments in whichinsulation 862 is applied to the proximal end of needle tip probe 802,it may be affixed at joint 863 via, e.g., epoxy, glue, solder, welding,brazing or any other method suitable for securing the insulation 862 toneedle tip probe 802, as will be appreciated by one of skill in the art.In either event, a lumen 864 is provided within insulation 862, throughwhich supply line 806 extends distally. Insulation 862 may be about 1 cmto about 20 cm in axial length, depending on the dimensions of needletip probe 802. At the distal end of the insulation 862, needle tip probe802 includes no insulation. This distal, uninsulated portion of needletip probe 802 is the ablation zone 822.

The combination of the proximal portion of needle tip probe 802 thatincludes insulation 862, and the uninsulated distal end of needle tipprobe 802 that forms ablation zone 822, restricts tissue freezing to thedistal tip of needle tip probe 802. Insulation 862 prevents freezedamage to tissue adjacent to the proximal end of needle tip probe 802.This allows insertion of the ablation zone 822 into, and destruction oftissue targets anywhere within a tissue or organ without damagingnon-targeted tissues adjacent to the insulation 862.

Insulation 862 may be any of a number of types of thermal insulationincluding but not limited to a permanent vacuum sleeve, drawing of anactive vacuum, an air gap lumen, low thermal capacity material, a gaslumen, and active thermoelectric heating. In various embodiments, any ofthe forgoing types of thermal insulation may be used to provideinsulation for catheter shaft 804 (FIGS. 16-24) and/or insulative tube870 (FIGS. 20-24) in addition to insulation 862.

As shown in FIGS. 23-24, device 800 may also include an accessoryinjection tube 849, running substantially parallel to return line 808,supply line 806, insulative tube 870 and catheter shaft 804. Accessoryinjection tube 849 may be disposed within insulative lumen 872, suchthat it is within catheter shaft 804 but outside of the insulative tube870. Alternatively, accessory injection tube 849 may be disposed withininsulative tube 870, such that it is within insulative tube 870 butoutside of the return line 808. Lastly, the accessory channel 849 may bedisposed within the wall of the catheter 804. As shown in, e.g., FIGS.23-24, accessory injection tube 849 may run the length of the device andmay terminate at a distal end at an exit portal 847 in needle tip probe802. Alternatively, accessory injection tube 849 may run the length ofthe device and may terminate at a distal end at an exit portal 847 atthe distal end of the catheter 804 (not shown). Accessory injection tube849 and exit portal 847 may be used in combination to deliver varioustreatment agents, e.g., anticancer agents, in conjunction with (i.e.,any one or more of before, during, or after) an ablation procedure.Accessory injection tube 849 is analogous in structure and function tothe accessory injection tubes 449 (FIGS. 4A-B), 557 (FIGS. 5 and 15),649 (FIGS. 6-7) and 849 (FIGS. 18-19), and exit portal 847 is analogousin structure and function to exit portal 447 (FIGS. 4A-B), 647 (FIGS.6-7) and 847 (FIGS. 18-19). In some embodiments the needle-tip probe 802may also consist of alternate tip shapes including blunt tip, lineartip, balloon tip or lasso tip shaped ablation zones.

D. Uses of the Cryoablation Catheter Device

The device 100, 400, 500, 600, 700, 800 is designed to provide thephysician with a tissue ablation zone by freezing the target cancer orunwanted tissue while reducing collateral damage to surroundingnon-targeted areas. The cryoablation device allows for more effective,reproducible, and controllable tissue ablation to treat diseased tissue.Further, the materials designated for manufacturing the apparatus of theinvention integrate stainless steel cryo-supply lines, polyamide returnlines as configured for cryo-temperatures, and any combination thereof.The umbilical is composed of flexible materials as known in the art butmay be modified to include plastics and polymeric combinations that areuseful in the field of medicine.

One embodiment of the cryoablation catheter incorporates the use of anendoscopic ultrasound (EUS) device such that the endoscopic catheterapparatus 100 can be passed through an accessory channel of an existingEUS device. Once the endoscopic catheter is inserted and manipulatedwithin proximity of a tissue site for treatment, the sheath is retractedto expose the needle cryoablation probe; and the probe is inserted intothe target tissue under ultrasound or other means of visualization.

For exemplary purposes and not limitation, the endoscopic ablationcatheter of the invention is utilized in ablating pancreatic tumortissue. The catheter is inserted through an accessory port of theultrasound endoscope through the stomach. Once positioned in the stomachnearest the adjacent pancreatic treatment area, the sheath is retractedand the probe inserted through the stomach wall into the pancreatictumor, simultaneously. The steps of retracting the sheath and theninserting the probe may occur in two separate steps as selected duringtreatment. The cryoprobe is then activated to freeze the target tissuesuch that the distal-most portion of the needle-tip probe creates anablation zone. The intermediary remainder of the needle that penetratesthe stomach wall does not freeze and does not damage extraneous tissueoutside the ablation zone. When freezing is completed, the tissue isallowed to thaw, either passively or actively via the integrated heatingelement within the probe. The thaw enables removal of the probe from thefrozen tissue mass without an extensive time delay. In this regard, theintegrated heating element within the tip of the cryoprobe can beactivated to accelerate tissue thawing or probe release from the tissue(rapid release). In addition to thawing the tissue, elevatedtemperatures can be achieved with the heating elements to ablateselected tissue, thereby allowing for the dual application ofcryoablation and hyperthermic (heat) ablation at a target tissue site.

In another aspect, the cryocatheter is inserted as described for aspecified cryo-treatment while a chemotherapeutic agent, a gene therapyagent or vector, a cell therapy agent, radiation, a vitamin, ananti-apoptotic or pro-apoptotic agent, a clotting agent or other desiredagent is administered to the target tissue region via one or moreintergraded tubes/channels. The agents can be injected manually orautomated with agent introduction points at the catheter handle orconsole. Addition of adjuvant or agent may occur prior to, during, orfollowing the cryo-treatment procedure. Furthermore, collection oftissue biopsies or fluid/tissue aspiration can be accomplished throughthe introduction of a biopsy needle or application of an aspirationvacuum (vacuum, pump, suction, syringe or other means of aspiration) viaone of the accessory channels.

As embodied in the invention, the device and procedure utilizes freezingin tandem with an endoscopic ultrasound device or any other type ofendoscope. Additionally the device and procedure can be combined withany other ablation or anti-cancer therapy through the intergradedaccessory tubes/channels within the cryocatheter assembly. The ECCdevice represents a significant advantage in the treatment of pancreaticand gastrointestinal cancers or other diseases.

Such benefits encompassed by the technology include the ability of theendoscopic compatible cryoablation probe/catheter to generate anultracold cryo-lesion, enhancing destruction of cancer cells whileminimizing side effects, and with the ability to rapidly ablate largerareas of pancreatic tissue. Furthermore, one embodiment of the inventionutilizes a method for applying cryoablation via endoscopic access to thetarget tissue which can include the pancreas, intestine, or otherportion of the gastrointestinal track. In another embodiment variationsof the device can also be used with other ultrasound or non-ultrasoundbased endoscope variants, including cystoscopes ureteroscopes,colorectal scopes, laryngeal scopes, etc. (i.e., endoscopes) for thetreatment of disease including cancerous and noncancerous lesions of theliver, stomach, colon, rectum, intestine, bladder, uterus, vagina,kidney, urethra, ureters, lungs, esophagus, etc.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritof the invention being indicated by the following claims. In addition,where this application has listed the steps of a method or procedure ina specific order, it may be possible, or even expedient in certaincircumstances, to change the order in which some steps are performed,and it is intended that the particular steps of the method or procedureclaim set forth here-below not be construed as being order-specificunless such order specificity is expressly stated in the claim.

1. A cryoablation device comprising: a catheter shaft; a cryogen returnline disposed within the catheter shaft; a cryogen supply line disposedwithin the cryogen return line, such that the cryogen supply line, thecryogen return line, and the catheter shaft are all substantiallycoaxial; a needle tip probe disposed at a distal end of the cryogenreturn line, wherein the cryogen supply line extends in a distaldirection beyond a distal end of the cryogen return line and into theneedle tip probe; an insulating tube disposed circumferentially aroundthe cryogen return line and within the catheter shaft; and an insulatinglumen circumferentially disposed around the cryogen return line, betweenan inner diameter of the catheter shaft and an outer diameter of theinsulating tube, wherein a position of the insulating tube is axiallyand rotationally fixed relative to the catheter shaft, and wherein aposition of the needle tip probe and the cryogen return line is axiallyand rotationally movable with respect to the insulating tube and thecatheter shaft.
 2. The cryoablation device of claim 1, wherein theinsulating lumen further comprises a vacuum sleeve, an actively drawnvacuum, an air gap, or a low thermal conductivity material.
 3. Thecryoablation device of claim 1, wherein the needle tip probe is affixedto an outer wall of the cryogen return line at the distal end of thecryogen return line.
 4. The cryoablation device of claim 1, wherein theneedle tip probe is affixed to an inner wall of the cryogen return lineat the distal end of the cryogen return line.
 5. The cryoablation deviceof claim 1, wherein the needle tip probe is affixed to the distal end ofthe cryogen return line using one of glue, epoxy, solder, welding, orbrazing.
 6. The cryoablation device of claim 1, wherein the needle tipprobe further includes insulation disposed on a proximal end thereof,and wherein the insulation disposed on the proximal end of the needletip probe defines an ablation zone on a distal end of the needle tipprobe for providing treatment.
 7. The cryoablation device of claim 6,wherein the insulation is affixed to the needle tip probe at a proximalend thereof.
 8. The cryoablation device of claim 1, wherein a ratio of avolume of the supply line to a volume of the return line is 1:1, 1:1.5,or 1:2.
 9. The cryoablation device of claim 1, wherein a ratio of across sectional area of the supply line to a cross sectional area of thereturn line is 1:1, 1:1.5, or 1:2.
 10. The cryoablation device of claim1, further comprising a heating element embedded within a wall of thecatheter shaft.
 11. The cryoablation device of claim 1, furthercomprising a deflection wire embedded within, or disposed adjacent to awall of the catheter shaft.
 12. The cryoablation device of claim 1,further comprising an accessory injection tube disposed within thecatheter shaft, such that the accessory injection tube is parallel tothe cryogen return line.
 13. The cryoablation device of claim 12,further comprising an exit portal in the needle tip probe, wherein theaccessory injection tube terminates at a distal end thereof at the exitportal, and the exit portal is configured to deliver a treatment agentto a treatment site, or to remove a tissue or a fluid from the treatmentsite.
 14. The cryoablation device of claim 12, wherein the insulatinglumen is circumferentially disposed around the return line, between aninner diameter of the catheter shaft and an outer diameter of theinsulative tube, and wherein the accessory injection tube is disposedwithin the insulating lumen.
 15. The cryoablation device of claim 12,wherein the accessory injection tube is disposed within the cathetershaft, such that the accessory injection tube is contained within thewall of the catheter.
 16. The cryoablation device of claim 12, furthercomprising an exit portal in the catheter or the insulating lumen,wherein the accessory injection tube terminates at a distal end at theexit portal, and the exit portal is configured to deliver a treatmentagent to a treatment site, or to remove a tissue or a fluid from thetreatment site.
 17. The cryoablation device of claim 1, wherein aproximal end of the catheter is affixed to a distal portion of a handleand the return line is affixed to the proximal portion of the handle,and wherein the catheter, the handle and the return line are configuredto allow simultaneous translational and rotational movement of thereturn line in relation to the catheter to expose the needle-tip probeand to cover the needle-tip probe.
 18. The cryoablation device of claim1, further comprising one or more thermal elements in the needle-tipprobe.
 19. The cyroblation device of claim 17, wherein the handleretracts and protracts the catheter relative to the needle-tip probe.20. The cryoablation device of claim 17, wherein the handle comprisescontrols to operate one or more of cryogen delivery, temperature, andthermal insulation.